Search PubMed⌕ Search

Biomedical subjects

M J Murray

Publications and source records attributed to M J Murray.

At least 37 records · Page 2Linked to original sources
PubMed2000

Concentrations of gentamicin in serum and bronchial lavage fluid after intravenous and aerosol administration of gentamicin to horses.

OBJECTIVE: To compare concentrations of gentamicin in serum and bronchial lavage fluid after IV and aerosol administration of gentamicin to horses. ANIMALS: 9 healthy adult horses. PROCEDURE: Gentamicin was administered by aerosolization (20 ml of gentamicin solution [50 mg/ml]) and IV injection (6.6 mg of gentamicin/kg of body weight) to each horse, with a minimum of 2 weeks between treatments. Samples of pulmonary epithelial lining fluid were collected by small volume (30 ml) bronchial lavage 0.5, 4, 8, and 24 hours after gentamicin administration. Serum samples were obtained at the same times. All samples were analyzed for gentamicin concentration, and cytologic examinations were performed on aliquots of bronchial lavage fluid collected at 0.5, 8, and 24 hours. RESULTS: Gentamicin concentrations in bronchial lavage fluid were significantly greater 0.5, 4, and 8 hours after aerosol administration, whereas serum concentrations were significantly less at all times after aerosol administration, compared with IV administration. Neutrophil counts in bronchial lavage fluid increased from 0.5 to 24 hours, regardless of route of gentamicin administration. CONCLUSIONS AND CLINICAL RELEVANCE: Aerosol administration of gentamicin to healthy horses resulted in gentamicin concentrations in bronchial fluid that were significantly greater than those obtained after IV administration. A mild inflammatory cell response was associated with aerosol delivery of gentamicin and repeated bronchial lavage. Aerosol administration of gentamicin may have clinical use in the treatment of bacterial bronchopneumonia in horses.

Administration, Inhalation↗
PubMed1999

Effects of roundabout on growth cone dynamics, filopodial length, and growth cone morphology at the midline and throughout the neuropile.

roundabout (robo) encodes an axon guidance receptor that controls midline crossing in the Drosophila CNS. In robo mutants, axons that normally project ipsilaterally can cross and recross the midline. Growth cones expressing Robo are believed to be repelled from the midline by the interaction of Robo and its ligand Slit, an extracellular protein expressed by the midline glia. To help understand the cellular basis for the midline repulsion mediated by Robo, we used time-lapse observations to compare the growth cone behavior of the ipsilaterally projecting motorneuron RP2 in robo and wild-type embyros. In wild-type embryos, filopodia can project across the midline but are quickly retracted. In robo mutants, medial filopodia can remain extended for longer periods and can develop into contralateral branches. In many cases RP2 produces both ipsilateral and contralateral branches, both of which can extend into the periphery. The growth cone also exhibits longer filopodia and more extensive branching both at the midline and throughout the neuropile. Cell injections in fixed stage 13 embryos confirmed and quantified these results for both RP2 and the interneuron pCC. The results suggest that Robo both repels growth cones at the midline and inhibits branching throughout the neuropile by promoting filopodial retraction.

Animals↗
PubMed1999

Expression of alpha6 and beta4 integrin subunits throughout the menstrual cycle: no correlation with uterine receptivity.

OBJECTIVE: To compare the expression of alpha6 and beta4 integrin subunit levels throughout the menstrual cycle in the endometrium of healthy women and infertile women. DESIGN: Prospective study. SETTING: An academic teaching hospital. PATIENT(S): Endometrium was collected from 58 women, including healthy subjects (n = 28) and patients undergoing diagnostic testing for infertility (n = 30). INTERVENTION(S): Endometrial biopsies were performed throughout the menstrual cycle in healthy women and infertile women. MAIN OUTCOME MEASURE(S): Immunohistochemical staining intensity of alpha6 and beta4 using the semiquantitative immunohistochemical score, compared using regression analysis and analysis of variance with Scheffé's correction. RESULT(S): There was no correlation between menstrual cycle phase and endometrial integrin subunit alpha6 or beta4 on glandular or luminal epithelium. Even women with identified luteal phase defects had indistinguishable patterns of expression for these integrin subunits during the window of implantation. CONCLUSION(S): The integrin subunits alpha6 and beta4 are expressed uniformly throughout the menstrual cycle on glandular and luminal epithelium. These integrins may have a housekeeping role in anchoring endometrial epithelium and do not appear to be useful markers of uterine receptivity.

Adult↗
PubMed1999

Population pharmacokinetics and pharmacodynamics of the anti-CD11a antibody hu1124 in human subjects with psoriasis.

The pharmacokinetics of hu1124, a human anti-CD11a antibody, were investigated in human subjects with psoriasis. CD11a is a subunit of LFA-1, a cell surface molecule involved in T cell mediated immune responses. Subjects received a single dose of 0.03, 0.1, 0.3, 0.6, 1, 2, 3, or 10 mg/kg of hu1124 intravenously over 1-3 hr. Blood samples were collected at selected times from 60 min to 72 days after administration. Plasma samples were assayed for hu1124 by ELISA, and pharmacokinetic analyses were performed on the drug plasma concentrations. As the dose of hu1124 was increased, the clearance decreased from 322 ml/day per kg at 0.1 mg/kg to 6.6 ml/day per kg at 10 mg/kg of hu1124. The plasma hu1124 concentration-time profile suggested that the clearance of hu1124 was saturable above 10 micrograms/ml. In addition, treatment with hu1124 caused a rapid reduction in the level of CD11a expression on CD3-positive lymphocytes (T cells) to about 25% of pretreatment levels. Regardless of the hu1124 dose administered, cell surface CD11a remained at this reduced level as long as hu1124 was detectable (> 0.025 microgram/ml) in the plasma. When hu1124 levels fell below 3 micrograms/ml, the drug was rapidly cleared from the circulation and expression of CD11a returned to normal within 7-10 days thereafter. In vitro, half-maximal binding of hu1124 to lymphocytes was achieved at about 0.1 microgram/ml and saturation required more than 10 micrograms/ml. One of the receptor-mediated pharmacokinetic/pharmacodynamic models which was developed describes the dynamic interaction of hu1124 binding to CD11a, resulting in the removal of hu1124 from the circulation and reduction of cell surface CD11a. The model accounts for the continually changing number of CD11a molecules available for removing hu1124 from the circulation based on prior exposure of cells expressing CD11a to hu1124. In addition, the model also accounts for saturation of CD11a molecules by hu1124 at drug concentrations of approximately 10 micrograms/ml, thereby reducing the clearance rate of hu1124 with increasing dose.

Animals↗
PubMed1999

Embryo implantation and tumor metastasis: common pathways of invasion and angiogenesis.

Implantation of the embryo is one of the last great mysteries of reproductive biology. There are striking similarities present between the behavior of invasive placental cells and that of invasive cancer cells. In this review, we propose that cellular mechanisms used by the cells of the placenta during implantation are reused by cancer cells to invade and spread within the body. Integrins and other cell adhesion molecules, extracellular matrix and matrix metalloproteinases all appear to be involved and are regulated by the complex endocrine, autocrine and paracrine milieu within the uterus. Angiogenesis is a common feature of both implantation and cancer spread. Endothelial cells also use similar cellular mechanisms during angiogenesis to digest the surrounding matrix, migrate and form new blood vessels. A better understanding of the mechanism of trophoblast invasion will likely lead to insights of various diseases of pregnancy such as preeclampsia. An appreciation of the maternal mechanisms to control this invasive behavior may likewise lead to a better understanding of metastatic cancer cells and lead to better methods to control their growth and spread within host tissues.

Cell Movement↗
PubMed1999

Monitoring cardiac function without the use of a pulmonary artery catheter.

Investigators have been trying to develop ways to measure cardiac function that are less invasive and more cost-effective than a pulmonary artery catheter. None of the technologies currently available are yet ready for routine use in assessing cardiac function in the operating room and in the intensive cardiac unit.

Journal Article↗
PubMed1999

Safety, acceptability and endoscopic findings in foals and yearling horses treated with a paste formulation of omeprazole for twenty-eight days.

A paste formulation of the H+,K(+)-ATPase inhibitor omeprazole was evaluated in Thoroughbred foals and yearlings for its safety and acceptability. Twenty foals age 11-16 weeks and 20 yearling horses age 15-17 months were included and gastroscopic examinations performed 1-3 days before and at the end of each trial. Lesions were scored on a scale of 0 to 3 and animals allocated based on endoscopic lesion score and sex, with 4 animals in each of 5 replicates. Dosages of 4 mg omeprazole/kg bwt or sham treatment were administered once daily for 28 days, from a syringe graduated in 50 lb (22.68 kg) increments, the amount of paste administered being rounded up to the nearest corresponding weight in pounds. Acceptability of the paste or sham treatment was assessed and recorded by the individual administering the treatment on the basis of the tolerance or resistance to insertion of the syringe into the mouth, administration of the paste and if the paste was swallowed or actively expelled by the animal. Safety was determined on the basis of daily observation recordings and physical examination findings during and at the conclusion of the trial. Treatment was judged to have been accepted for all 420 doses of omeprazole paste and all 140 sham doses given to foals during the trial and for 418/420 doses of paste and all 140 sham doses given to yearlings. Two doses of paste were entirely rejected by yearlings. On the initial endoscopic examination, lesions were observed in the gastric squamous epithelial mucosa in 4 foals and 3 yearlings, and single small, superficial erosions were seen in the gastric glandular mucosa of 2 foals. On the second examination there were small, superficial erosions in the squamous mucosa in 3 foals and 2 yearlings, multi-focal superficial erosions in 1 foal and 1 yearling, and 1 foal had large areas of erosion extending from the margo plicatus toward the dorsal fundus. No lesions in the glandular mucosa were seen in foals or yearlings. There were no significant differences (P < 0.05) in lesion scores between the beginning and the end of the trials in the omeprazole-treated or sham-treated groups of foals or yearlings. A paste formulation of omeprazole, administered at a dose of 4 mg/kg bwt once daily for 28 days, was determined to be highly acceptable to the foals and yearlings we studied, and no adverse effects attributable to the medication were noted.

Administration, Oral↗
PubMed1998

The utility of hemodynamic measurements acquired by pulmonary artery catheterization.

BACKGROUND: Concerns about the utility of pulmonary artery catheters (PAC) stimulated us to assess the impact of one of the parameters measured by the PAC, the pulmonary capillary wedge pressure (PCWP), on our clinical practice. METHODS: The PCWP was recorded at 4- to 6-hour intervals on 50 patients for the first 48 hours following aortic aneurysm repair. We then reviewed the patients' records looking for evidence that the PCWP measurements were used to guide therapy. For the purpose of the study, we anticipated the administration of diuretics for PCWP > or =218 mm Hg and volume resuscitation for PCWP < or =8 mm Hg. Data were correlated using Pearson rank correlation coefficient using a P < 0.05 to determine statistical significance. RESULTS: Patients with PCWPs <8 mm Hg were more likely to be treated with volume resuscitation (P < 0.05). There was no other correlation between PCWP measurements and fluid or pharmacologic management. CONCLUSIONS: Data derived from the PAC are infrequently used to guide therapy in patients who undergo abdominal aortic reconstructive surgery.

Aged↗
PubMed1998

No difference exists in the alteration of circadian rhythm between patients with and without intensive care unit psychosis.

OBJECTIVE: To determine if a difference exists in the circadian rhythm entrainment between patients with and without intensive care unit (ICU) psychosis. DESIGN: Retrospective chart reviews from 149 consecutive patients admitted to our ICU during the period of January 1993 to August 1993. Twelve patients with a history of mental illness or alcohol or substance abuse were excluded from the study. SETTING: A 20-bed surgical ICU at a large teaching hospital. PATIENTS: Patients who remained in the ICU for a minimum of 2 days after undergoing thoracic or vascular operations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hourly temperature and urine output were ascertained from the patient records. The time of temperature and urine output nadir was used as a marker of circadian rhythm. Of the 137 patients included in the study, 17 (12.4%) developed ICU psychosis as defined by standard criteria. The time of temperature nadir was randomly distributed around the clock for each group. Cosinar rhythmometry analysis of temperature data showed a lack of circadian rhythm entrainment in most patients up to the third postoperative day. No statistically significant difference exists in the deviation of such impairment between the groups. CONCLUSION: Either patients who develop ICU psychosis have an increased sensitivity to an alteration of their circadian rhythm, or ICU psychosis develops independent of circadian rhythm abnormalities.

Adaptation, Physiological↗
PubMed1998

The early critical phase of severe head injury: importance of apnea and dysfunctional respiration.

BACKGROUND: Apnea is a known response of concussive head injury. Hypoxic or ischemic brain injury has been documented in a high percentage of severe head injury deaths. The respiratory response after head injury remains poorly defined, however, and its contribution to hypoxic or ischemic mechanisms after severe head injury is unknown. METHODS: Eighteen anesthetized but spontaneously breathing rats were subjected to fluid percussion head injury of varying severities. Respiratory rate and volume of air were recorded before and after injury with a Hans Rudolph/Varadyne pneumotach differential pressure transducer and graphically measured. Postmortem inspection of the brains was performed. RESULTS: Apnea and subsequent respiratory dysfunction are directly proportional to the magnitude of energy delivered to the brain. Higher energy results in a dysfunctional or absent respiratory response, probably attributable to failure or disorganized function of the medullary respiratory center. CONCLUSION: This study for the first time graphically depicts the respiratory response after head injury. Higher energy delivered to the brain directly correlates with a markedly abnormal respiratory response that probably contributes significantly to subsequent hypoxic or ischemic brain injury. The absence of the space-occupying hematoma or gross parenchymal disruption suggests that in the clinical setting many of these patients may otherwise have survivable head injury if rescued by early ventilatory assistance.

Animals↗
PubMed1998

Clinical assessment of gas exchange in mature horses.

There are limited methods of assessing pulmonary function in horses at rest. We developed clinical techniques to measure gas exchange efficiency in horses and evaluated 3 groups of horses that were 1) asymptomatic based on auscultation with rebreathing, transtracheal aspirate cytology, and thoracic radiographs (n = 6), 2) asymptomatic at rest but symptomatic with rebreathing (n = 11) and 3) symptomatic at rest (n = 9). Blood samples were obtained from the transverse facial artery and jugular vein. Maximal end-tidal CO2 tension (PETCO2) was measured by an infrared capnograph through a facemask. Alveolar O2 tension, dead space fraction (V(D)/V(T)), and physiological shunt fraction (Q(S)/Q(T)) were calculated using standard formulae. Arterial O2 tension in Group 1 horses (mean +/-s.d.103+/-3 mmHg) was significantly higher than in Group 2 or Group 3 horses. Q(S)/Q(T) in Group 1 horses (0.37+/-0.98%) was significantly lower than in Group 2 and Group 3 horses. Mean +/-s.d.V(D)/V(T) in Group 1 horses (-18.2+/-3.1) was significantly lower than Group 3 horses but not Group 2 horses.

Aging↗
PubMed1998

Effects of gender on resting leg blood flow: implications for measurement of regional substrate oxidation.

These studies were designed to examine whether the respiratory quotient (RQ) of leg tissue (primarily skeletal muscle) would increase to a greater degree in women than in men during meal ingestion. We found that mean leg and systemic RQ values were similar in men under both basal and fed conditions, whereas the agreement was poor in women. In women, leg RQ values tended to be greater than the systemic RQ, whereas splanchnic RQ values tended to be lower than the systemic RQ. The possibility that measurement imprecision accounted for the different findings in women could not be excluded because the arteriovenous blood O2 differences were almost twice as great in men as in women (53.7 +/- 5.4 vs. 28.6 +/- 2.9 ml of O2/l, respectively; P < 0.01), as were venoarterial blood CO2 differences. The smaller arteriovenous differences in women appeared to limit our ability to accurately measure their leg RQ values. O2 uptake relative to leg fat-free mass (FFM) was not different between men and women, whereas leg blood flow relative to leg FFM was greater in women than in men (55 +/- 3 vs. 39 +/- 2 ml.kg FFM-1.min-1, respectively; P < 0.001). These findings were confirmed by examining data from other studies conducted in our laboratory to create a larger data set. We conclude that resting leg blood flow in women is greater (relative to FFM) than in men, making it more difficult to accurately measure leg RQ in women.

Adult↗
PubMed1998

Serum thyroid peroxidase autoantibodies, thyroid volume, and outcome in breast carcinoma.

The prevalence of thyroid peroxidase autoantibodies (TPO.Ab) was assessed in patients with either breast carcinoma or benign breast disease, and its association with disease outcome in breast carcinoma was studied. TPO.Ab were detected by direct RIA in serum from 121/356 (34.0%) of patients with breast carcinoma, compared with 36/194 (18.5%) of controls (P < 0.001); and in 31/108 (28.7%) with benign breast disease, compared with 12/88 (13.6%) of controls (P < 0.05). Survival analysis in a group of 142 women with breast carcinoma demonstrated that TPO.Ab titres > or = 0.3 U/mL were associated with a significantly better disease-free [relative risk (RR) = 1.84, P < 0.05] and overall survival (RR = 3.46, P < 0.02), compared with those who were TPO.Ab-negative. Better outcome associated with higher TPO.Ab titres was confined to those who had thyroid volumes within the intermediate range (10.1-18.8 mL) and did not further enhance the good outcome recorded when volumes were < or = 10.0 mL or > 18.8 mL. Multivariate survival analysis showed that both TPO.Ab and thyroid volume were independently associated with prognosis in breast carcinoma and that RRs for disease-free survival were of a similar order of magnitude to well-established prognostic indices such as axillary nodal status or tumor size. These findings supply evidence that manifestations of thyroid autoimmunity are associated with a beneficial effect on disease outcome in breast carcinoma and provide the strongest evidence to date of a biological link between breast carcinoma and thyroid disease.

Adult↗
PubMed1998

Idiopathic distal esophageal dilation in a southern black rhinoceros (Diceros bicornis minor).

An adult female southern black rhinoceros (Diceros bicornis minor) experienced intermittent periods of regurgitation while eating, suggesting an esophageal disorder. Endoscopy for evaluation of the trachea, esophagus, and stomach revealed a 30-mm nasopharyngeal orifice with associated recess located in the caudodorsal pharynx and a 10-cm dilated segment of the distal esophagus that was presumably the cause of regurgitation. Dietary management of esophageal dilation through short-term utilization of a "soft feed" program successfully eliminated the regurgitation. This is the first report of esophageal dysfunction in a rhinoceros.

Animals↗